Scholarlink

<p>Vulvar squamous cell carcinoma (VSCC) comprises biologically distinct subtypes with divergent molecular profiles and clinical behaviors. In this study, we performed comprehensive genomic profiling of 48 primary VSCCs, integrating mutational and copy number data with HPV status and clinicopathological parameters. Tumors were stratified into HPV-associated (HPVA), HPV-independent (HPVI), and a third proposed subgroup characterized by HPV negativity and wild-type TP53 status. Overall, 650 somatic mutations were identified, with <i>TP53</i>, <i>TERT</i> promoter, <i>NOTCH1</i>, <i>PIK3CA</i>, and <i>CDKN2A</i> being the most frequently altered genes. HPVA VSCCs exhibited a higher mutational burden and enrichment of <i>PIK3CA</i>, <i>NOTCH1</i>, and <i>MLL2</i> mutations, consistent with APOBEC-driven mutagenesis. HPVI VSCCs showed frequent <i>TP53</i>, <i>TERTp</i>, and <i>CDKN2A</i> mutations, along with an age-related mutational signature. Copy number alterations were more common in HPVI tumors, with recurrent amplifications in <i>CCND1</i>, <i>FGF3/4/19</i>, and CDK pathway genes. Six VSCCs lacked both HPV association and <i>TP53</i> mutations, supporting the existence of a third molecular subtype, with frequent <i>TERTp</i> mutations and limited additional alterations. No significant survival differences were observed between subtypes, although nodal status remained prognostically relevant. These findings refine the molecular taxonomy of VSCC, support the recognition of a third genomic subgroup, and highlight subtype-specific therapeutic targets.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Comprehensive genomic profiling of vulvar squamous cell carcinoma reveals subtype-specific mutational landscapes

  • 期刊论文

  • 发表日期：

    2026年5月11日

查看全文
  • M. Choschzick,
  • L. Hoesli,
  • C. Stergiou,
  • J. H. Rüschoff

摘要

Vulvar squamous cell carcinoma (VSCC) comprises biologically distinct subtypes with divergent molecular profiles and clinical behaviors. In this study, we performed comprehensive genomic profiling of 48 primary VSCCs, integrating mutational and copy number data with HPV status and clinicopathological parameters. Tumors were stratified into HPV-associated (HPVA), HPV-independent (HPVI), and a third proposed subgroup characterized by HPV negativity and wild-type TP53 status. Overall, 650 somatic mutations were identified, with TP53, TERT promoter, NOTCH1, PIK3CA, and CDKN2A being the most frequently altered genes. HPVA VSCCs exhibited a higher mutational burden and enrichment of PIK3CA, NOTCH1, and MLL2 mutations, consistent with APOBEC-driven mutagenesis. HPVI VSCCs showed frequent TP53, TERTp, and CDKN2A mutations, along with an age-related mutational signature. Copy number alterations were more common in HPVI tumors, with recurrent amplifications in CCND1, FGF3/4/19, and CDK pathway genes. Six VSCCs lacked both HPV association and TP53 mutations, supporting the existence of a third molecular subtype, with frequent TERTp mutations and limited additional alterations. No significant survival differences were observed between subtypes, although nodal status remained prognostically relevant. These findings refine the molecular taxonomy of VSCC, support the recognition of a third genomic subgroup, and highlight subtype-specific therapeutic targets.